RT Journal Article
SR Electronic
T1 <sup>11</sup>C-Dihydrotetrabenazine PET of the Pancreas in Subjects with Long-Standing Type 1 Diabetes and in Healthy Controls
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 382
OP 389
DO 10.2967/jnumed.108.054866
VO 50
IS 3
A1 Robin Goland
A1 Matthew Freeby
A1 Ramin Parsey
A1 Yoshifumi Saisho
A1 Dileep Kumar
A1 Norman Simpson
A1 Joy Hirsch
A1 Martin Prince
A1 Antonella Maffei
A1 J. John Mann
A1 Peter C. Butler
A1 Ronald Van Heertum
A1 Rudolph L. Leibel
A1 Masanori Ichise
A1 Paul E. Harris
YR 2009
UL http://jnm.snmjournals.org/content/50/3/382.abstract
AB Type 2 vesicular monoamine transporter (VMAT2), found in the brain, is also expressed by β-cells of the pancreas in association with insulin. Preclinical experiments suggested that 11C-dihydrotetrabenazine PET–measured VMAT2 binding might serve as a biomarker of β-cell mass. We evaluated the feasibility of 11C-dihydrotetrabenazine PET quantification of pancreatic VMAT2 binding in healthy subjects and patients with long-standing type 1 diabetes. Methods: 11C-Dihydrotetrabenazine PET was performed on 6 patients and 9 controls. VMAT2 binding potential (BPND) was estimated voxelwise by using the renal cortex as reference tissue. As an index of total pancreatic VMAT2, the functional binding capacity (the sum of voxel BPND × voxel volume) was calculated. Pancreatic BPND, functional binding capacity, and stimulated insulin secretion measurements were compared between groups. Results: The pancreatic mean BPND was decreased in patients (1.86 ± 0.05) to 86% of control values (2.14 ± 0.08) (P = 0.01). In controls, but not in patients, BPND correlated with stimulated insulin secretion (r2 = 0.50, P = 0.03). The average functional binding capacity was decreased by at least 40% in patients (P = 0.001). The changes in functional binding capacity and BPND were less than the near-complete loss of stimulated insulin secretion observed in patients (P = 0.001). Conclusion: These results suggest that 11C-dihydrotetrabenazine PET allows quantification of VMAT2 binding in the human pancreas. However, BPND and functional binding capacity appear to overestimate β-cell mass given the near-complete depletion of β-cell mass in long-standing type 1 diabetes, which may be due to higher nonspecific binding in the pancreas than in the renal cortex.